The goal of this work was to examine whether neural stem cells could restore memory in an animal model of neurodegenerative diseases, much as they have been found to affect locomotor activity. The animal model employed involved targeted destruction of CA1 pyramidal cells of the hippocampus of transgenic mice in which a tetracycline inducible promoter system is used to trigger the expression of diphtheria toxin A-chain in neurons containing calmodulin kinase II alpha. Expression of the toxin could be controlled sufficiently well to destroy the CA1 subfield (and the pyramidal cells in particular), while sparing other brain regions (e.g., cortex).

Implantation of neural stem cells into the hippocampus resulted in localized engraftment in the toxin-induced animals, but rather diffuse engraftment in various regions, including the cortex, of controls. Histological examination revealed that the stem cells differentiate into neurons, oligodendrocytes, and astrocytes. At three months post-transplantation of the stem cells, a significant improvement was observed in memory involved in the recollection of a place, which is a hippocampus-dependent task, but not in memory related to object recognition, which is dependent on the cortex. The improvement correlated well with a significant increase in the synaptic density of the CA1 region of the stem-cell treated hippocampus.

The results suggest that neural stem cells may have therapeutic value against neurodegenerative diseases that impair memory. However, this study also demonstrated that transplanted stem cells have higher rates of survival in control animals’ hippocampus than in the ablated model. Whether this is related to a change in the microenvironment or an experimental limitation will require further research. And that raises another question: Will the processes that precipitate a neurodegenerative disease need to be quieted or repaired for neural stem cells to offer a long-term therapeutic solution?